Epidemiological surveys indicate that an average of 50% of the adult population of the United States (US) has gingivitis and that gingivitis can lead to a number of life threatening illnesses such as heart disease. Since gingivitis is caused by plaque and plaque is composed of various kinds of bacteria, in theory antimicrobial agents should be effective against gingivitis. Most anti-plaque compounds, e.g. triclosan, chlorohexidene and fluorine, are halogenated. Marine microorganisms, which can generate compounds that integrate halogens such as chlorine and bromine, can thus be an important resource for the discovery of anti-plaque compounds. Recently 4,800 extracts derived from 150 marine microorganisms were screened for anti-microbial activity against - Haemophilus actinomycetemcomitans, Actinomyces viscosus, and Streptococcus mutans. The extract of one organism, APP214, was found to have excellent inhibitory and bactericidal activity against these microorganisms. The specific aims of this proposal are to isolate, identify and characterize (in terms of antimicrobial efficacy and toxicity) the bioactive components derived from APP214. In Phase II, medicinal and combinatorial chemistry will be performed on the candidate compound(s) to maximize effectiveness and substantivity against orally-relevant microorganisms. In Phase III, the lead anti-plaque compound will be commercialized with an industrial partner, such as Tom's of Maine, Gillette or Colgate-Palmolive. PROPOSED COMMERCIAL APPLICATIONS: There is currently no truly efficacious anti-gingivitis product that is also both convenient to use and appealing to the consumer. A product that is effective and substantive against oral biofilms (dental plaque) will have a significant market potential in the United States and internationally.